Name: Nitroglycerin (Nitro-Bid)
Class: Antianginal Agent (Organonitrate)
Mechanism: Converted to NO ® activation of cytosolic guanylate cyclase ® cGMP ® activation of cGMP-dependent protein kinase ® smooth muscle relaxation ® vasodilation. Greater effect in veins & large arteries than in resistance vessels ® ¯¯ preload, ¯ afterload ® ¯ work ® ¯ O2 demand. Inhib. of platelet fxn.
Absorption: Sublingual preferred. IV. Oral ® 1st pass Metabolism, low bioavail. Buccal/transdermal ® slow absorption.
Dist.:
Metabolism.: Hepatic (glutathione-organic nitrate reductase), extra-hepatic. Plasma clearance >> C.O.
Excretion, t½: Renal. 3 min. Short duration of action (20-30 min.).
Toxicity/S.E.s: Orthostatic hypotension, tachycardia, severe throbbing headache, dizziness, flushing, syncope. C/i w/elevated ICP.
Utility: Treat angina. Subling. not suitable for maintenance therapy. IV for severe recurrent unstable angina. Oral/buccal/transdermal for prophylaxis, but may ® tolerance.
Special Features: 8+ hr. breaks necessary to avoid tolerance from slow absorp.